Huangqi-Danshen Decoction Ameliorates Adenine-Induced Chronic Kidney Disease by Modulating Mitochondrial Dynamics

Abstract

Chronic kidney disease (CKD) is a leading public health problem with high morbidity and mortality. However, the therapies remain limited. Traditional Chinese medicine (TCM) has been used for treating kidney disease for thousands of years and is an effective alternative treatment for CKD patients in China and other Asian countries. In the present study, we aimed to investigate the effect and mechanism of Huangqi-Danshen decoction (HDD), a TCM herbal decoction, on treating CKD. CKD rat model was induced by adding 0.75% adenine to the diet for 4 weeks. HDD extract was administrated orally to CKD rats at the dose of 4.7 g/kg/d for consecutive 4 weeks in adenine-induced CKD rats. Kidney function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The pathological changes of kidney tissues were observed by periodic acid-Schiff (PAS) and Masson's trichrome staining. The proteins expression of renal fibrosis and mitochondrial dynamics were determined and quantified by Western blot analysis. CKD rats showed obvious decline in renal function as evidenced by increased levels of Scr and BUN, which were blunted by HDD treatment. HDD could also improve tubular atrophy and interstitial fibrosis of CKD rats. Moreover, HDD downregulated fibronectin, type IV collagen, and α-smooth muscle actin expression in CKD rats. Furthermore, mitochondrial dynamics was disturbed in CKD rats, which manifested as increased mitochondrial fission and decreased mitochondrial fusion. HDD treatment restored mitochondrial dynamics in CKD rats by repressing dynamin-related protein 1 and Mid 49/51 expression, promoting mitofusin 2 expression, and suppressing optic atrophy 1 proteolysis. In conclusion, HDD could significantly retard CKD progression through modulating mitochondrial dynamics.

Jian-Pi-Yi-Shen Decoction Relieves Renal Anemia in 5/6 Nephrectomized Rats: Production of Erythropoietin via Hypoxia Inducible Factor Signaling

“…Previous pharmacological studies have supported that JPYS can improve renal function and kidney injury in CKD rats [9–11] and can stimulate the transcriptional expression of EPO in cultured kidney HEK293T cells [12]. Besides, the extract of Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma deriving from JPYS also has been found to ameliorate adenine-induced CKD rats [13]. These findings confirm the beneficial role of JPYS for treatment of CKD anemia.…”

Metabolomics Analysis Reveals the Protection Mechanism of Huangqi–Danshen Decoction on Adenine-Induced Chronic Kidney Disease in Rats

“…According to TCM theory, Qi deficiency and blood stasis (Qi-Xu-Xue-Yu) runs through the CKD process (Liu et al, 2019). HDD is composed of Astragali Radix (Huang-qi) served as replenishing Qi and Salviae Miltiorrhizae Radix et Rhizoma (Dan-shen) served as activating blood, and is one of the most common used drug pair in clinical treatment of CKD.…”

“…All the botanical names are recorded and can be validated using . The HDD water extract was prepared as previously described (Liu et al, 2019). High-performance liquid chromatography–mass spectrometry (HPLC-MS) analysis was conducted to confirm the quality of the HDD extract, as indicated in Supplementary Figure S1 .…”

“…According to TCM theory, HDD possesses the efficacies of replenishing Qi and activating blood (Yi-Qi-Huo-Xue), which helps delay the progress of CKD. The previous pharmacological study has showed the renoprotective effect of HDD in adenine-induced CKD rats (Liu et al, 2019). However, the underlying mechanism of HDD on CKD is less known.…”

Jian-Pi-Yi-Shen Regulates EPO and Iron Recycling Protein Expressions in Anemic Rats with Chronic Kidney Disease: Accumulation of Hypoxia Inducible Factor-2α via ERK Signaling

“…Traditional Chinese medicine (TCM) plays a unique role in the treatment of many diseases, and a growing body of evidence has shown that TCM is increasingly being used for preventing CKD and anemia [8][9][10]. Jian-Pi-Yi-Shen improved the anemia symptoms by increasing the serum EPO level and hypoxia inducible factor (HIF)-α protein in 5/6 nephretomized rats [11,12].…”